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Aberrant basal cell clonal dynamics shape early lung carcinogenesis

Gómez-López, Sandra; Alhendi, Ahmed SN; Przybilla, Moritz J; Bordeu, Ignacio; Whiteman, Zoe E; Butler, Timothy; Rouhani, Maral J; ... Janes, Sam M; + view all (2025) Aberrant basal cell clonal dynamics shape early lung carcinogenesis. Science , 388 (6752) , Article eads9145. 10.1126/science.ads9145. Green open access

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Abstract

Preinvasive squamous lung lesions are precursors of lung squamous cell carcinoma (LUSC). The cellular events underlying lesion formation are unknown. Using a carcinogen-induced model of LUSC with no added genetic hits or cell type bias, we find that carcinogen exposure leads to non-neutral competition among basal cells, aberrant clonal expansions, and basal cell mobilization along the airways. Ultimately, preinvasive lesions develop from a few highly mutated clones that dominate most of the bronchial tree. Multi-site sequencing in human patients confirms the presence of clonally related preinvasive lesions across distinct airway regions. Our work identifies a transition in basal cell clonal dynamics, and an associated shift in basal cell fate, as drivers of field cancerization in the lung.

Type: Article
Title: Aberrant basal cell clonal dynamics shape early lung carcinogenesis
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1126/science.ads9145
Publisher version: https://doi.org/10.1126/science.ads9145
Language: English
Additional information: This version is the author accepted manuscript. It is made available under a Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10209551
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